1. Field of the Invention
The present invention is directed to a method for controlling the volume flow into or out of an osmotic micropump and an apparatus thereof.
2. Description of the Related Art
Micropumps are important for micro-fluidics, micro-administration of liquids and micro-injection in analytics and medical technology. Mechanical devices for driving the volume flow by electromagnetic or electrostatic forces are known, so are pumps driven by diffusion or electro-osmosis. Micropumps known as evaporation pumps and osmotic pumps are driven by diffusion. In both cases the volume flow is created by the help of a diaphragm that is permeable to the solvent.
In evaporation pumps the evaporation-caused capillary tension within the pores of the diaphragm is transduced to a flow path. They can be applied as suction pumps only and, therefore, their use in micro-fluidics is sensitive to cavitation. An example for an evaporation pump is described in EP 1167757 A3. To prevent access of non-volatile substances to the diaphragm the suction is provided by a completely evaporating liquid and a mobile separation element is applied to transduce the suction to the liquid that is to be pumped. The separation element can be, for example, a separated liquid, a movable piston, or a flexible membrane.
In electro-osmotic pumps the liquid in the pores of the semipermeable diaphragm is moved by an electric current through the diaphragm, the driving force being created at the electric double layers within the pores. This requires fixed charges in the pores of the applied diaphragm. Electro-osmotic pumps can be used in micro-fluidics for distinct purposes. Their advantage over evaporation or osmotic pumps consists in good controllability of the flow rate. Their disadvantages are low energy efficiency, high waste heat and inability to create a high pressure difference.
In osmotic pumps the volume flow is caused by diffusion of the permeable solvent within the semipermeable diaphragm or within a diffusion layer at its surface.
Osmotic pumps have the advantage of high energy efficiency. By their help a difference in chemical potential can be transformed into volume work without strong heat development. They can be applied without electrical power supply for generation of suction and pressure and they are able to overcome high back pressure. They can be used for delivery of liquids, as has been described for example in US 2001/0047161 and U.S. Pat. No. 4,320,758. In these pumps a solvent, e.g. water, permeates through a semipermeable diaphragm into a chamber that is filled with the solution of non-permeable solvent and wherein the pressure can be increased due to the osmotically driven volume flow. This chamber may be built either as a closed working chamber with expandable volume that is covered by a flexible membrane, or as an open delivery chamber, from which the solution is driven through an outlet. Osmotic micro-pumps are commercially available and can be used, e.g., for delivery of drugs into the interstitium or veins.
The liquid leaving the delivery chamber of an osmotic pump contains the osmotically effective solute. This is not a disadvantage as a matter of principle, since it is possible to bring a movable separation element between this liquid and the liquid to be administrated, as described e.g. in DE 4106624 A1. The entrance of the solvent into the solution within the expandable working chamber or within the open delivery chamber causes progressive solute dilution and, in consequence, a progressive decrement of the flow rate. A high volume and/or a mixing device in the working or delivery chamber would be required to minimize this decrement. However, the dilution effect can be prevented by filling the working chamber with salt crystals or other soluble solid material, which is dissolved at solvent entrance and generates a saturated solution of the solute in equilibrium with its solution (Theeuwes F., Yum S. I. Principles of the design and operation of generic osmotic pumps for the delivery of semisolid or liquid drug formulations. Ann. Biomed. Eng. 4 (4), 343-354 (1976), Yu-Chuan Su, Liwei Lin and Alert P. Pissano, J. of Microelectromechanical Systems 11, 736-741, 2002). Osmotic pumps using a solution equilibrium in this way are able to deliver a volume flow with constant velocity against high back pressure. Nevertheless, the volume delivered with constant rate remains limited. It is given by the ratio between the mass of the solid solute in the chamber and the concentration of its saturated solution. In the case of sodium chloride it is not much larger than the volume of the delivery chamber. The delivered liquid contains the solute at its saturation concentration, although a much lower concentration is sufficient for creating enough pressure for most applications. The limited ratio between the volume of the saturated solution that can be delivered and the volume of the pump is a technical shortcoming with respect to miniaturisation.
The task for the present invention consists in the provision of a method and a device for controlling a volume flux driven by an osmotic micropump with a delivery chamber, which is not limited by the volume of the delivery chamber.